A Single Blind, Two-Stage Dose Finding Study to Evaluate the Safety, Tolerability and Efficacy of a Single Liproca® Depot Injection Into the Prostate in Patients With Localized Prostate Cancer, Assigned to Active Surveillance Who Are at High Risk for Disease Progression (Followed by an Open Label Extension With a Repeat Injection (Optional)).

A Single Blind, Two-Stage Dose Finding Study to Evaluate the Safety, Tolerability and Efficacy of a Single Liproca® Depot Injection into the Prostate in Patients with Localized Prostate Cancer,Assigned to Active Surveillance who are at High Risk for Disease Progression (followed by an Open Label Extension with a Repeat Injection (Optional))

开始日期2017-05-12

申办/合作机构

LIDDS AB

[+1]

NCT02341404

/ Completed临床2期

An Open, Single Dose, Antitumour Effect Study of 2-hydroxy-flutamide as a Controlled Release Product (Liproca Depot), Injected Into the Prostate in Patients With Localized Prostate Cancer

The primary aim of the study was to characterize and quantify the histopathological changes in the surgical specimens obtained in patients undergoing prostatectomy in addition to imaging changes (MRI) following a single injection of Liproca Depot in patients with localized prostate cancer.

开始日期2012-05-01

申办/合作机构

LIDDS AB

[+1]

NCT00913263

/ Completed临床1/2期

An Open, Single and Multiple Dose, Efficacy and Safety Proof of Principle Study of Liproca Depot, a Controlled Release Formulation of 2-hydroxyflutamide, Injected Into the Prostate in Patients With Localized Prostate Cancer

The primary objective was to evaluate efficacy of a single dose of Liproca Depot in patients with localized prostate cancer. Primary efficacy variable was the proportion of patients showing PSA nadir. 24 Caucasian men, with a mean age at inclusion of 68.4 years, with localized prostate cancer were injected once with a ready made paste including 600 mg 2-hydroxyflutamide (Liproca Depot) into the site of the prostate where the tumour was localized. The patient was monitored for prostate-specific antigen (PSA) for maximum 6 months or to progression within this time period. The primary endpoint showed interesting results with high success rate (83%), i.e. proportion of patients (Responders) that reached plasma PSA nadir.

开始日期2009-06-01

申办/合作机构

LIDDS AB

100 项与 2-Hydroxyflutamide 相关的临床结果

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100 项与 2-Hydroxyflutamide 相关的转化医学

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100 项与 2-Hydroxyflutamide 相关的专利（医药）

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392

项与 2-Hydroxyflutamide 相关的文献（医药）

2025-06-01·TOXICOLOGY IN VITRO

Cross-species comparisons of plasma binding and considerations for data evaluation

Article

作者: Watson, Scott L ; Lynn, Scott G ; Patel, Purvi R ; Yueh, Yun Lan ; Schultz, Irvin R ; Black, Sherry R ; Wetmore, Barbara A ; Matten, Sharlene R

The US Environmental Protection Agency is increasingly employing new approach methods (NAMs), including in vitro plasma binding and hepatocyte clearance experiments to collect chemical-species specific data. This paper presents data from plasma binding experiments using rapid equilibrium dialysis (RED) devices and plasma from humans, rats, and rainbow trout with a 4-h incubation time. A total of 54 chemicals, utilizing two concentrations, were tested across the three species resulting in 238 chemical-species specific datasets. Mass balance controls for chemical plasma stability and dialysis system recovery were used to evaluate the datasets and almost 40 % of the datasets (92/238 datasets) produced quantitative measurements. Cross-species comparisons and evaluations of the impact of physicochemical properties on chemical-assay performance were also evaluated. Comparisons of human-rat plasma binding revealed rat plasma generally demonstrated higher f_up values for chemicals than human. While f_up values in trout plasma were frequently lower than rat or human plasma. A comparison with literature data was performed and correlations between plasma binding, expressed as fraction unbound in plasma (f_up), and log K_ow across all three species indicate that the strongest relationship occurs at log K_ow values between 1.5 and 4. The obtained datasets exhibited a wide range of behaviors, emphasizing the need for a robust approach to data quality assessment. The broader analysis of f_up values indicates that chemicals with log K_ow > 4.5 will be highly bound (f_up ≤ 0.0001), difficult to measure, and have low reproducibility across laboratories, suggesting that use of different methods may be needed across different physicochemical properties.

2024-11-01·PHYTOMEDICINE

Metabolomic profiling integrated with molecular exploring delineates the action of Ligusticum chuanxiong hort. on migraine

Article

作者: Peng, Cheng ; Xing, Ziwei ; Peng, Fu ; Li, Dan ; Wan, Feng ; Chen, Yu

INTRODUCTION:

Ligusticum chuanxiong hort. (Chuanxiong, CX) is a well-known traditional edible-medicinal herb, especially in brain diseases. However, there is a lack of studies focusing on the action of CX in metabolites of migraine.

HYPOTHESIS/PURPOSE:

To investigate the action of the aqueous extract of CX (LCH) on nitroglycerin (NTG)-induced migraine.

METHODS:

The effects and mechanisms of LCH on migraine were evaluated in NTG-induced mice and rats. Laser speckle contrast imaging was performed to detect the cerebral blood flow. Metabolomic analysis in serum and mass spectrometry imaging in brain tissue from NTG-induced rats were conducted to explore the metabolites. The techniques including RT-qPCR, immunohistochemistry, and immunofluorescence were employed to estimate the molecular changes.

RESULTS:

Totally, 1480 metabolites were identified, among which, 50 and 49 differential metabolites were identified by t-test, fold change, and VIP score for NTG vs. CON and LCH+NTG vs. NTG, respectively. Next, 13 common real difference metabolites were revealed by comparative analysis, and KEGG annotation and enrichment analysis showed that the glutathione (GSH) metabolism pathway played important roles in migraine, whereas the glutamate could be metabolized to γ-glu-cys and converted to GSH. Molecular exploring further confirmed that LCH treatment increased the expression of essential components of GSH synthetase, such as GCLC and GCLM, and elevated the expression levels of Nrf-2 and its downstream targets including HO1 and NQO1. Moreover, the mass spectrometry imaging results found that LCH treatment promoted the synthesis of GSH and the spatial distribution of glucose as well as ATP metabolites to normal levels.

CONCLUSION:

To sum up, the present study firstly reveals that LCH plays a therapeutic role for migraine through glucose-glutamate-Nrf-2 axis, which might represent a promising approach in the development of advanced therapeutic strategies for migraine, and the LCH may be an effective drug or dietary supplement for relieving headache.

2024-08-01·Molecular oncology

TAS3681, an androgen receptor antagonist, prevents drug resistance driven by aberrant androgen receptor signaling in prostate cancer

Article

作者: Shohei Yoshida ; Mizutani, Hiroya ; Okajima, Shigeo ; Daisuke Kajiwara ; Masanori Asai ; Yuki Tanaka ; Asai, Masanori ; Ryoto Fujita ; Minamiguchi, Kazuhisa ; Tanaka, Yuki ; Keisuke Yamamura ; Manabu Tayama ; Seki, Masanao ; Yamamura, Keisuke ; Masanao Seki ; Kazuhisa Minamiguchi ; Tayama, Manabu ; Hiroya Mizutani ; Fujita, Ryoto ; Shigeo Okajima ; Kajiwara, Daisuke ; Yoshida, Shohei

Second‐generation androgen receptor (AR) signaling inhibitors (ARSIs), such as abiraterone and enzalutamide, prolong the life of patients with castration‐resistant prostate cancer (CRPC). However, patients receiving ARSIs ultimately develop resistance through various complex mechanisms, including AR mutations, constitutively active AR‐splice variants (AR‐Vs), and AR overexpression. Here, we characterized a novel AR pure antagonist, TAS3681, which inhibits AR transcriptional activity and downregulates AR‐full length (AR‐FL) and AR‐Vs. TAS3681 reduced the protein levels of AR‐FL and AR‐Vs including AR‐V7 in enzalutamide‐resistant cells (SAS MDV No. 3‐14), in vitro and in vivo, showing strong antitumor efficacy in an AR‐V7‐positive xenograft model. In AR‐overexpressing VCaP (prostate cancer) cells, conversely to enzalutamide, TAS3681 effectively suppressed cell proliferation and downregulated AR expression. Importantly, TAS3681 blocked the transcriptional activity of various mutant ARs, including mutations F877L/T878A and H875Y/T878A, which confer resistance to enzalutamide, and V716M and H875Y mutations, which confer resistance to darolutamide. Our results demonstrate that TAS3681 suppresses the reactivation of AR signaling, which causes resistance to ARSIs, via a newly identified mechanism of action. Therefore, TAS3681 could be a new therapeutic option for CRPC treatment.

项与 2-Hydroxyflutamide 相关的新闻（医药）

2021-02-07

·GlobeNewswire

European Urology Focus has accepted a scientific article describing LIDDS Phase IIb study results with Liproca® Depot

UPPSALA, SWEDEN – LIDDS AB (publ) announces that a scientific article will be published in the highly ranked European Urology Focus describing LIDDS clinical Phase IIb study, LPC-004, and its clinical results. The study met both primary and secondary endpoints by confirming efficacy and safety with Liproca Depot given as intraprostatic injection in low- and intermediate risk prostate cancer patients. “We are pleased that this manuscript is accepted in a highly recognized scientific paper and the results further validates NanoZolid® as being an innovative technology platform,” said Monica Wallter, CEO of LIDDS. Liproca Depot, which comprises the NanoZolid technology combined with an antiandrogen drug (2-hydroxyflutamide) injected into the prostate, met both the primary and secondary endpoints in the study. Efficacy was shown by a maintained PSA decrease over 6 months, lower prostate volume and unchanged or improved MRI results. No hormonal side effects were shown. LIDDS concludes that Liproca® Depot can be a new potential local treatment that is effective in controlling cancer for intermediate risk patients under “Active Surveillance”. The manuscript has the title “Liproca Depot – A new antiandrogen treatment for active surveillance patients" and is planned to be published on the European Urology Focus webpage during February. “The results confirm that Liproca® Depot can offer a completely novel approach to complement active surveillance in intermediate risk prostate cancer patients. Liproca® Depot is well tolerated without the hormonal side effects otherwise associated with anti-androgen therapy and is equally easy to administer as performing a prostate biopsy. Liproca® Depot treatment could contribute to the benefit of prostate cancer patients in the future, says Professor Laurence Klotz, a world leading expert and one of the study investigators and Professor at the University of Toronto Division of Urology. The NanoZolid® technology has during the last years been shown to enable a local controlled release of a wide range of drugs following a single injection, resulting in stable and pharmacologically relevant effects over the desired time-period, to overcome issues with systemic adverse effects or local frequent treatments. LIDDS has active projects where NanoZolid is successfully combined with cytotoxic- and immune modulating compounds with the intention to treat solid cancer tumors. About the LPC-004 study The LPC-004 study was a single blind, two-part dose finding study aimed to determine the highest tolerable dose of Liproca® Depot and to determine the level of PSA reduction for part II patients at month 5 (primary endpoints). The study was conducted at specialist urology clinics in Canada, Lithuania and Finland. The study involved 61 patients diagnosed with localized non-aggressive prostate cancer who were on Active Surveillance. Patients were followed for six months to assess response and tolerability. Following the LPC-004 study, a voluntary open label extension study was initiated offering patients a second injection of Liproca® Depot once the patient’s PSA level had returned to its pre-treatment level. Results showed that 50 % of the patients in the open label extension study remained at low PSA levels for at least 10 months from their first Liproca® Depot injection and were therefore not treated with a second injection. For more information, please contact: Monica Wallter, CEO, +46 (0)737 07 09 22, e-mail: monica.wallter@liddspharma.com

100 项与 2-Hydroxyflutamide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	2-Hydroxyflutamide	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
局限性前列腺癌	临床2期	芬兰	LIDDS AB	2012-05-01
局限性前列腺癌	临床2期	瑞典	LIDDS AB	2012-05-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00913263 (2-HOF, CTgov)	临床1/2期	局限性前列腺癌	24	Liproca (Part I)	淵網製廠遞廠齋淵簾鏇 = 選鏇構網鹽獵襯鏇襯築醖襯齋構顧淵鑰齋糧鏇 (範網選壓蓋衊壓鹽蓋範, 簾醖淵構鹹壓淵醖衊淵 ~ 範艱壓築鹽獵鹽鏇遞積) 更多	-	2015-01-19
				Liproca (Group 1)	膚鑰鏇網壓衊築顧獵遞 = 壓繭簾壓積廠鬱廠窪鹹鏇憲蓋憲觸鹹餘構蓋鑰 (餘積襯製淵範鏇淵鬱窪, 膚鑰蓋築齋淵衊鹽淵齋 ~ 餘醖淵鬱願鏇獵壓範衊) 更多